This grant application titled, IL29 and IL28B variants associated with periodontal disease pathogenesis, is a Mentored Patient-Oriented Research Career Development Award (K23) proposal under the guidance of Steven Offenbacher (UNC, School of Dentistry). The training and research plan represent outgrowths of my clinical training and emerging translational research; the research project centers on the most pressing current clinical dilemma faced in Periodontal Pathogenesis: genetic predisposition. Results obtained from a genome- wide association study (GWAS) identified genes important for several aspects of periodontal disease, particularly IL29 and IL28B, which are involved with modulating the innate and adaptive immune system in response to bacterial and viral challenge. The overall goals of this career development award are to provide the candidate with the necessary didactic and experiential learning to facilitate his transition to an independent investigator and to determine the clinical relevance of minor allelic variants of IL28B and IL29 with the expression of chronic periodontitis. Aim 1 will be used to determine the impact of SNP variants on periodontal disease expression and local inflammatory response during stent-induced biofilm overgrowth. This model, which is a contemporary version of the classic experimental gingivitis model, will be used to evaluate the influence of IL28B and IL29 SNP variants on the clinical response to biofilm overgrowth, as compared to the dominant allelic variants. Aim 2 will evaluate in vitro the impact of SNP variants on cell-mediated, innate inflammatory response. This reverse translational aim will evaluate the impact of the minor allelic SNP variants of IL28B and IL29 on cytokine responses of dendritic cells. To accomplish the goals of this proposal, the candidate has access to a unique collaborative environment including Periodontists, Epidemiologist, Microbiologists, Immunologists, and a Biostatistician from the resources of the UNC Schools of Dentistry, Medicine, and Gillings Public Health. There are programmatic links between these schools and individuals that will allow on-going interactions with a very diverse group of clinicians and researchers who focus on the oral health. The primary mentor, Steven Offenbacher is a Professor of Periodontology at the School of Dentistry. He has an established record of NIH funding through NIDCR with expertise in most areas of periodontal research (both clinical and basic science) including education, systemic diseases, implantology, osteoimmunology, andgenetics. The Research Advisory Committee members, Ricardo Teles, Kari North, Jennifer Webster-Cyriaque, and John Preisser, each bring distinct strengths to the Committee. Dr. Teles has expertise in clinical research, periodontal disease pathogenesis, and microbial and host-derived biomarkers. Dr. North expertise includes Genetic Epidemiology and Statistical Genetics. Dr. Webster-Cyriaque is an immunologist with experience with molecular pathogenesis in oral disease and an established record of NIH funding. Dr. Preisser's main collaborative research is in dentistry, including oral epidemiology and biological mechanisms of periodontal disease. He has collaborated with the Offenbacher group for several years. The members of the Research Advisory Committee are accomplished researchers in their respective fields and will provide insights into the development and execution of the research strategy plan, and most importantly provide mentoring through my developmental career plan. The goals during the this five-year award period are to become an independent scientist, with deeper understanding of research design, the ethical treatment of human subjects, and the role of genomics on periodontal disease pathogenesis. The five-year framework of the grant will provide the tools and skills to become an independent researcher. The candidate will use the training and research accomplished in this award to prepare for a competitive R01 grant application.